Preliminary results of a prospective assessment of androgen receptor splice variants in mCRPC patients undergoing androgen receptor targeted agents.

Abstract

246 Background: Different treatment options for metastatic castrate resistant prostate cancer (mCRPC) are currently available, including Androgen Receptor Targeted Agents (ARTA) and Taxane based chemotherapy. However, selection criteria aiming to drive the therapeutic choice in this setting are lacking, and no standardized therapeutic sequence is validated. In our institution, a prospective study testing predictive value of circulating tumor cells (CTC) in patients (pts) receiving a first line ARTA for mCRPC is currently ongoing (PRIMERA). Here, we present preliminary results from the first enrolled cohort. Methods: Pts affected by mCRPC eligible for Androgen Deprivation Therapy (ADT) plus ARTA were prospectively enrolled and underwent baseline determination of androgen-receptor splice variant 7 (AR-V7) and androgen-receptor-full length (ARFL) variants on CTC at baseline (ARTA start). Fisher Exact Test was conducted to explore the correlation between baseline features and CTC detection rate. Results: Overall, 26 pts were enrolled and baseline results are available for 13 pts. CTC were found in 5 (38.5%) pts. No significant difference was reported in terms of CTC detection probability for pts with high vs low burden of disease according to CHARTEED definition (p=0.42), neither for pts with PSA at CRPC diagnosis < or > 10 ng/ml, (p=0.2). However, a PSA > 10 ng/ml at ADT start in metastatic hormone sensitive setting (mHSPC) was significantly related to CTC detection probability (p=0.01). AR-V7 variants were found in 1 out 5 (20%) CTC-positive pts. Conclusions: PSA at ADT start may significantly be related to CTC detection rate. CTC detection could be particularly useful in pts with a high burden of disease at the beginning of systemic therapy. Metastatic disease could remain dormant until development of CRPC status, with consequent release of increased amount of CTC, more likely to be detected in this setting. AR-V7 expression was found in 20% of CTC positive pts, in line with literature data.[Table: see text]